We are using the FEATURE software, in collaboration with Russ Altman at Stanford University, on the enolase superfamily to characterize special features within this unique class of proteins which share a common fold, the alpha/beta or TIM barrel. The FEATURE package creates descriptions of protein microenvironments using physical and chemical properties at multiple levles of detail including features at the atomic, chemical group, residue, and secondary structural levels in order to recognize sites in three dimensional protein structures. We are performing a comparative analysis of distantly related proteins at the tertiary structural level. We are using molecular modeling tools to determine the variable and conserved elements of the members of the enolase superfamily from comparisons and superposition of structures. From these data ,we will develop a structural template for the superfamily that will allow us to differentiate the structural elements that mediate common function from those that give rise to specificity. Such templates can then be used for many purposes such as re-engineering enzymes.